循环肿瘤细胞(CTCs)是一类存在于外周血中稀有的肿瘤细胞，与肿瘤的远处转移密切相关，针对此类细胞的研究可以阐明肿瘤转移的重要机制。我们前期针对CTCs的研究发现，CTCs存在上皮间质化（EMT）特点，EMT是肿瘤侵袭转移一个重要过程，肿瘤细胞通过EMT获得侵袭能力，结合CTCs研究EMT的机制，可以对恶性肿瘤侵袭转移获得更为全面的认识；LncRNA在EMT调控过程中起关键性作用，LncRNA-SNHG16上调可以诱导肿瘤细胞的EMT，且可能通过发挥ceRNA功能特异性调节YAP1；同时YAP1表达改变可直接影响SNHG16的表达水平。我们依据前期工作基础，以机制研究为出发点，动物模型、临床样本为落脚点，系统阐明SNHG16/YAP1正反馈回路调控EMT的作用机制，以及SNHG16/YAP1正反馈回路对CTCs转移潜能的影响，进一步阐明CTCs EMT在结直肠癌肝转移中的作用和机制。

Circulating tumor cells (CTCs) from primary cancers hold great potential that initiates distant metastasis. Although CTCs are extraordinarily rare cancer cells, our established techniques could effectively enrich CTCs for further analysis of blood-borne metastatic mechanism. Previous studies by us showed that CTCs exhibited characteristics of epithelial-mesenchymal transition (EMT), and the number of EMT-CTCs was positively associated with advanced stage of colorectal cancer. EMT has been considered as a critical process for tumor cells to gain invasive phenotype. Therefore, studies focusing on CTCs’ EMT would achieve a more comprehensive spectrum of metastatic mechanism. LncRNA(Long non-coding RNA) have been demonstrated to act as master regulators of some key players that are involved in many important biological pathways of EMT. Our preliminary findings suggested that SNHG16 act as a novel player in modulating tumor cell EMT through regulating YAP1 expression, and YAP1 may play its role of transcriptional coactivator in the regulation of SNHG16. YAP1 and SNHG16 may form a positive feedback loop to promote EMT-mediated colorectal cancer invasion and metastasis. Based on our preliminary results, this project aims to systematically determine the essential in vitro and in vivo roles for SNHG16/YAP1 positive feedback loop-mediated tumor cell EMT in colorectal CTCs formation and invasion, finally identifying the underlying mechanisms responsible for these observations. These novel results obtained from this work would reveal mechanistic insights to highlight the importance of SNHG16/YAP1 positive feedback loop-mediated EMT in colorectal CTCs’ metastatic potential, and further illuminate the role and molecular mechanism of CTCs EMT in liver metastasis of colorectal cancer.